Cardiovascular research
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Cardiovascular research · Jul 2006
Monocyte-specific Bcl-2 expression attenuates inflammation and heart failure in monocyte chemoattractant protein-1 (MCP-1)-induced cardiomyopathy.
Infiltrating inflammatory cells within the myocardium have been shown to be apoptotic, but the significance of apoptotic inflammatory cells to the development of cardiomyopathy remains undefined. Transgenic mice with cardiac-specific expression of MCP-1 exhibit extensive apoptosis of infiltrating mononuclear cells and develop heart failure. Here, we tested the hypothesis that in vivo selective inhibition of apoptosis of infiltrating mononuclear cells would preserve cardiac structure and function and improve survival in this murine model. ⋯ These results demonstrate that apoptosis of infiltrating mononuclear cells plays a detrimental role in the development of heart failure in this murine model, suggesting that modulation of apoptosis of infiltrating mononuclear cells may be of clinical benefit in heart failure.
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Cardiovascular research · May 2006
ReviewPostconditioning: reduction of reperfusion-induced injury.
Reperfusion has the potential to introduce additional injury that is not evident at the end of ischaemia per se, i.e. reperfusion injury. Reperfusion injury is expressed as endothelial and microvascular dysfunction, impaired blood flow, metabolic dysfunction, cellular necrosis, and apoptosis. There is an impressive array of mechanisms contributing to reperfusion injury. ⋯ Hence, postconditioning marshals a variety of endogenous mechanisms that operate at numerous levels and target a broad range of pathological mechanisms. Two clinical studies in patients with acute myocardial infarction have demonstrated that postconditioning was effective in reducing infarct size. Postconditioning indirectly supports the concept of reperfusion injury in animal models of ischaemia-reperfusion and in patients, and exerts cardioprotection that is equivalent to that of ischaemic preconditioning.
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Cardiovascular research · Apr 2006
Bone marrow molecular alterations after myocardial infarction: Impact on endothelial progenitor cells.
Standard drugs post-myocardial infarction (MI) such as angiotensin converting enzyme (ACE) and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) increase levels of endothelial progenitor cells (EPC). However, potential underlying mechanisms have not yet been investigated. ⋯ Increased ROS and impaired MMP-9 activity in bone marrow likely contribute to reduced EPC mobilization in the early post-infarction phase. ACE inhibition or statin treatment increased EPC levels with distinct drug-specific effects on bone marrow molecular alterations.
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Cardiovascular research · Nov 2005
Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner.
Patients with congestive heart failure (CHF) suffer considerable morbidity and mortality despite advances in therapy. Treatment with erythropoietin (Epo) has shown promise in CHF patients, yet its mechanisms of action remain elusive. Endothelial progenitor cells (EPC) contribute to postnatal angiogenesis and vasculogenesis, and Epo was shown to promote EPC mobilization. We explored the effect of chronic treatment with Epo on the numbers and functional properties of EPC in CHF patients. ⋯ Chronic Epo treatment is associated with an increase in the adhesive and proliferative properties of circulating EPC in patients with CHF.
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Cardiovascular research · Sep 2005
Increased SR Ca2+ cycling contributes to improved contractile performance in SERCA2a-overexpressing transgenic rats.
Heart failure is associated with reduced function of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) but increased function of sarcolemmal Na+/Ca2+ exchanger (NCX), leading to decreased SR Ca2+ content and loss of frequency-potentiation of contractile force. We reported that SERCA2a-overexpression in transgenic rat hearts (TG) results in improved contractility. However, it was not clear whether TG have improved contractility due to frequency-dependent improved SR Ca2+ handling. ⋯ In summary, SERCA2a-overexpression improved contractility in a frequency-dependent way due to increased SR Ca2+ loading whereas transsarcolemmal Ca2+ fluxes were decreased.